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5. Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986–2020

Author

Nduva, George M, primary, Otieno, Frederick, additional, Kimani, Joshua, additional, Sein, Yiakon, additional, Arimide, Dawit A, additional, Mckinnon, Lyle R, additional, Cholette, Francois, additional, Lawrence, Morris K, additional, Majiwa, Maxwell, additional, Masika, Moses, additional, Mutua, Gaudensia, additional, Anzala, Omu, additional, Graham, Susan M, additional, Gelmon, Larry, additional, Price, Matt A, additional, Smith, Adrian D, additional, Bailey, Robert C, additional, Medstrand, Patrik, additional, Sanders, Eduard J, additional, Esbjörnsson, Joakim, additional, and Hassan, Amin S, additional

Published
2023
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7. Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study

Author

N'Buna, Babetida, Biague, Antonio J., Biai, Ansu, Camara, Cidia, Esbjörnsson, Joakim, Jansson, Marianne, Karlson, Sara, Lindman, Jacob, Medstrand, Patrik, Månsson, Fredrik, Norrgren, Hans, Palm, Angelica A., Özkaya Sahin, Gülsen, da Silva, Zacarias José, Wilhelmson, Sten, Kvist, Anders, da Silva, Zacarias J, Andersson, Sören, Fenyö, Eva Maria, Isberg, Per-Erik, Biague, Antonio J, Palm, Angelica A, and Rowland-Jones, Sarah L

Published
2019
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8. Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986–2020.

Author

Nduva, George M, Otieno, Frederick, Kimani, Joshua, Sein, Yiakon, Arimide, Dawit A, Mckinnon, Lyle R, Cholette, Francois, Lawrence, Morris K, Majiwa, Maxwell, Masika, Moses, Mutua, Gaudensia, Anzala, Omu, Graham, Susan M, Gelmon, Larry, Price, Matt A, Smith, Adrian D, Bailey, Robert C, Medstrand, Patrik, Sanders, Eduard J, and Esbjörnsson, Joakim

Subjects
RALTEGRAVIR, INFECTIOUS disease transmission, DRUG resistance, HIV, REVERSE transcriptase inhibitors, INTEGRASE inhibitors
Abstract

Background Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. Methods HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. Results Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2–16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016–20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011–15), but dropped to 6.5% (2016–20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000–08], indicating propagation over 12 years. Conclusions Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya. [ABSTRACT FROM AUTHOR]

Published
2024
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13. TEMPORAL TRENDS AND TRANSMISSION DYNAMICS OF PRE-TREATMENT HIV-1 DRUG RESISTANCE WITHIN AND BETWEEN RISK GROUPS IN KENYA, 1986-2020.

Author

Nduva, George M., primary, Otieno, Frederick, additional, Kimani, Joshua, additional, Sein, Yiakon, additional, Arimide, Dawit A., additional, McKinnon, Lyle R., additional, Cholette, Francois, additional, Lawrence, Morris K., additional, Majiwa, Maxwell, additional, Masika, Moses, additional, Mutua, Gaudensia, additional, Anzala, Omu, additional, Graham, Susan M., additional, Gelmon, Larry, additional, Price, Matt A., additional, Smith, Adrian D., additional, Bailey, Robert C., additional, Medstrand, Patrik, additional, Sanders, Eduard J., additional, Esbjornsson, Joakim, additional, and Hassan, Amin S., additional

Published
2023
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14. HIV-2 as a model to identify a functional HIV cure

Author

Esbjörnsson, Joakim, Jansson, Marianne, Jespersen, Sanne, Månsson, Fredrik, Hønge, Bo L., Lindman, Jacob, Medina, Candida, da Silva, Zacarias J., Norrgren, Hans, Medstrand, Patrik, Rowland-Jones, Sarah L., and Wejse, Christian

Published
2019
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20. Impact of Persistent Organic Pollutants on AIDS progression and all-cause mortality. A longitudinal study in HIV-2 infected individuals in Guinea-Bissau

Author

Lindman, Jacob, primary, Ström, Kajsa, additional, Månsson, Fredrik, additional, Biague, Antonio, additional, Silva, Zacarias José da, additional, Esbjörnsson, Joakim, additional, Jansson, Marianne, additional, Medstrand, Patrik, additional, Jakobsson, Kristina, additional, and Norrgren, Hans, additional

Published
2022
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22. Intra-Patient Evolution of HIV-2 Molecular Properties

Author

Palm, Angelica A., primary, Esbjörnsson, Joakim, additional, Kvist, Anders, additional, Månsson, Fredrik, additional, Biague, Antonio, additional, Norrgren, Hans, additional, Jansson, Marianne, additional, and Medstrand, Patrik, additional

Published
2022
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25. High Level of HIV Drug Resistance and Virologic Nonsuppression Among Female Sex Workers in Ethiopia: A Nationwide Cross-Sectional Study

Author

Arimide, Dawit Assefa, primary, Amogne, Minilik Demissie, additional, Kebede, Yenew, additional, Balcha, Taye T., additional, Adugna, Fekadu, additional, Ramos, Artur, additional, DeVos, Joshua, additional, Zeh, Clement, additional, Agardh, Anette, additional, Chih-Wei Chang, Joy, additional, Björkman, Per, additional, and Medstrand, Patrik, additional

Published
2022
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26. Hierarchical Clustering and Trajectory Analyses Reveal Viremia-Independent B-Cell Perturbations in HIV-2 Infection

Author

Johansson, Emil, Kerkman, Priscilla, Scharf, Lydia, Lindman, Jacob, Szojka, Zsófia I., Månsson, Fredrik, Biague, Antonio, Medstrand, Patrik, Norrgren, Hans, Buggert, Marcus, Karlsson, Annika C., Forsell, Mattias N. E., Esbjörnsson, Joakim, and Jansson, Marianne

Subjects
Infectious Medicine, B-cell phenotype, viremia, HIV-2, CD95, HIV-1, Mikrobiologi inom det medicinska området, immune perturbations, Infektionsmedicin, T-bet, Microbiology in the medical area
Abstract

Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and proliferating T-bet+CD95highCD27+CD71+ memory B-cells in viremic HIV-1 (p < 0.001 and p < 0.001, respectively), viremic HIV-2 (p < 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.

Published
2022

28. Size distribution of exhaled aerosol particles containing SARS-CoV-2 RNA.

Author

Alsved, Malin, Nygren, David, Thuresson, Sara, Fraenkel, Carl-Johan, Medstrand, Patrik, and Löndahl, Jakob

Subjects
SARS-CoV-2, MICROBIOLOGICAL aerosols, AEROSOLS, AIRBORNE infection, RNA
Abstract

SARS-CoV-2 in exhaled aerosols is considered an important contributor to the spread of COVID-19. However, characterizing the size distribution of virus-containing aerosol particles has been challenging as high concentrations of SARS-CoV-2 in exhaled air is mainly present close to symptom onset. We present a case study of a person with COVID-19 who was able to participate in extensive measurements of exhaled aerosols already on the day of symptom onset and then for the following three days. Aerosol collection was performed using an eight-stage impactor while the subject was breathing, talking and singing, for 30 min each, once every day. In addition, nasopharyngeal samples, saliva samples, room air samples and information on symptom manifestations were collected every day. Samples were analyzed by RT-qPCR for detection of SARS-CoV-2 RNA. SARS-CoV-2 RNA was detected in seven of the eight particle size fractions, from 0.34 to >8.1 µm, with the highest concentrations found in 0.94–2.8 µm particles. The concentration of SARS-CoV-2 RNA was highest on the day of symptom onset, and declined for each day thereafter. Our data showed that 90% of the exhaled SARS-CoV-2 RNA was found in aerosol particles <4.5 µm, indicating the importance of small particles for the transmission of COVID-19 close to symptom onset. These results are important for our understanding of airborne transmission, for developing accurate models and for selecting appropriate mitigation strategies. [ABSTRACT FROM AUTHOR]

Published
2023
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34. INTRAHOST EVOLUTION OF THE HIV-2 CAPSID CORRELATES WITH PROGRESSION TO AIDS

Author

Boswell, Michael Terence, primary, Nazziwa, Jamirah, additional, Kuroki, Kimiko, additional, Palm, Angelica, additional, Karlson, Sara, additional, Mansson, Fredrik, additional, Biague, Antonio Jaime, additional, da Silva, Zacarias, additional, Onyango, Clayton, additional, de Silva, Thushan, additional, Jaye, Assan, additional, Norrgren, Hans, additional, Medstrand, Patrik, additional, Jansson, Marianne, additional, Maenaka, Katsumi, additional, Rowland-Jones, Sarah, additional, and Esbjornsson, Joakim, additional

Published
2021
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38. Drug Resistance in HIV-Positive Adults During the Initial Year of Antiretroviral Treatment at Ethiopian Health Centers

Author

Reepalu, Anton, Arimide, Dawit A, Balcha, Taye T, Yeba, Habtamu, Zewdu, Adinew, Medstrand, Patrik, and Björkman, Per

Subjects
primary health care, AcademicSubjects/MED00290, drug resistance, tuberculosis, HIV, Ethiopia, Major Articles
Abstract

Background The increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition. Methods Participants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis. Results Among 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis. Conclusions Among adults receiving health center–based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.

Published
2021

46. An endogenous retroviral long terminal repeat is the dominant promoter for human [beta]1,3-galactosyltransferase 5 in the colon

Author

Dunn, Catherine A., Medstrand, Patrik, and Mager, Dixie L.

Subjects
Retroviruses -- Research, Science and technology
Abstract

LTRs of endogenous retroviruses are known to affect expression of several human genes, typically as a relatively minor alternative promoter. Here, we report that an endogenous retrovirus LTR acts as one of at least two alternative promoters for the human [beta]1,3-galactosyltransferase 5 gene, involved in type I Lewis antigen synthesis, and show that the LTR promoter is most active in the gastrointestinal tract and mammary gland. Indeed, the LTR is the dominant promoter in the colon, indicating that this ancient retroviral element has a major impact on gene expression. Using colorectal cancer cell lines and electrophoretic mobility-shift assays, we found that hepatocyte nuclear factor 1 (HNF-1) binds a site within the retroviral promoter and that expression of HNF-1 and interaction with its binding site correlated with promoter activation. We conclude that HNF-1 is at least partially responsible for the tissue-specific activation of the LTR promoter of human [beta]1,3-galactosyltransferase 5. We demonstrate that this tissue-specific transcription factor is implicated in the activation of an LTR gene promoter.

Published
2003

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